c-fms expression is a molecular marker of human acute myeloid leukemias

The c-fms protooncogene product was identified as the CSF-1 or M-CSF receptor, a polypeptide growth factor that plays a major role in myelomonocytic differentiation. This led us to look for expression of c-fms in fresh acute myeloid leukemia (AML) cells, using Northern blot analysis. c-fms expression was found in the leukemic cells of 28 AML patients, regardless of their stage of differentiation, which was assessed in the French-American-British (FAB) classification. However, the level of c-fms expression was especially high in AML of the M5 stage. High levels of expression were not accompanied by either amplification or rearrangements of the c-fms gene in AML cell DNAs. In contrast, c-fms expression was not found in acute lymphoid leukemias, whether of T or B origin. Thus, c-fms expression appears as a specific molecular marker of leukemogenesis in the myeloid lineage.     

Cell marker analysis in acute monocytic leukemias.

Leukemic cells from nine cases of acute monocytic leukemia (AMoL) were characterized by multiple differentiation markers. Cells in most cases were phagocytic, carried an Fc receptor, and stained positively for alpha-naphthyl acetate esterase but negatively for naphthol AS-D chloroacetate esterase. However, subtle differences in marker expression were observed which suggested different degrees of leukemic cellular maturation or activation. Cell marker analysis proved to be a useful adjunct to conventional morphology in confirming the diagnosis and the recognition of the neoplastic cells in AMoL, and may ultimately provide insight into the functional state of these cells.     

Factors related to prognosis and relapse in acute myelomonocytic and monocytic leukemias (M4 and M5)

To analyse the factors which were related to prognosis at first examination and early diagnosis of relapse in complete remission phase, 26 patients with acute myelomonocytic leukemia (M4) and acute monocytic leukemia (M5) were investigated. There was a tight relationship between age and remission rate in patients with M4 and M5. Six of M4 with eosinophilia (M4Eo) patients revealed 83.3% as remission rate with good prognosis in the survival curve. LDH level of them was lower than other patients significantly. In order to diagnose relapse before clinical manifestations, it was useful to follow up number of mature monocytes (over 600/microliters) in the peripheral blood.     

Oncoplacental protein SP1--a constitutive and inducible late differentiation marker of the human myelomonocytic lineage

The oncoplacental protein SP1 is found in large quantities in human placenta, amniotic fluid, and pregnancy serum. Low levels have been reported in association with malignancy but also in healthy nonpregnant individuals. By indirect immunofluorescence, fluorescence-activated cell sorting, and immunoprecipitation we here demonstrate the presence of SP1 both on the surface and in the cytoplasm of human granulocytes but not in earlier myeloid progenitor cells in bone marrow. Lymphocytes did not contain the protein, and only trace amounts could be found in the cytoplasm of blood monocytes. A major glycoprotein with an apparent mol wt of 90,000 was obtained by immunoprecipitation of surface-labeled granulocytes. Cultivated blood monocytes, while adhering to surfaces or forming multinuclear giant cells, displayed a strong membrane and cytoplasmic expression of SP1. Treatment of the myeloid leukemia cell line ML-2 with tetraphorbol acetate (TPA) strongly induced SP1 in the membrane and cytoplasm as revealed by immunofluorescence and polyacrylamide gel electrophoresis (PAGE) of immunoprecipitates from lysates of surface radiolabeled cells. The induction of synthesis of SP1 in TPA-treated cells was confirmed by immunoprecipitation from lysates of cells metabolically labeled with 35S-methionine. Human lymphoblastoid and erythroleukemic cell lines did not express SP1 either before or after induced differentiation. Thus SP1 provides a late differentiation marker for the myelomonocytic lineage and is strongly induced during macrophage differentiation or by TPA treatment of ML-2 cells.     

5-Aza-2''-deoxycytidine induces terminal differentiation of leukemic blasts from patients with acute myeloid leukemias

In this study, the effects of 5-aza-2'-deoxycytidine on differentiation of human leukemic cells in primary suspension culture are reported for the first time. Morphological and functional differentiation was induced in cells from two acute monoblastic leukemias and two of three acute myeloid leukemias following repeated exposures to 1 mumol/L 5-aza- 2'-deoxycytidine. The observation that nontoxic concentrations of the drug are able to induce the in vitro differentiation of both monoblastic and myeloblastic leukemic cells into mature elements may encourage the exploitation of the differentiating properties of 5-aza- 2'-deoxycytidine in chemotherapy protocols for acute non-lymphoblastic leukemias.     

Expression of CD56/NCAM on hematopoietic malignant cells. A useful marker for acute monocytic and megakaryocytic leukemias.

We investigated the expression of CD56 (a neural cell adhesion molecule, NCAM) and CD57 in various hematopoietic and non-hematopoietic malignant cells, using Leu-19 and Leu-7 monoclonal antibodies. Although both molecules are commonly defined as a natural killer cell marker, we found that CD56 was highly expressed on blasts from patients with acute monocytic (4/6) and megakaryocytic (3/3) leukemias. In the latter, FACS two-color analysis revealed that leukemic megakaryoblasts simultaneously expressed CD56 and platelet-related antigens. Among leukemic cell lines, one myelocytic, three monocytic, and two megakaryocytic lines were positive for CD56. On the other hand, except for one large granular lymphocytic leukemia and one multiple myeloma cell line, none of the lymphoid leukemia cell lines or lymphoblasts from patients with acute lymphocytic leukemia (ALL) (0/15), non-Hodgkin's lymphoma (NHL) (0/2), and central nervous system (CNS) leukemia (0/2) reacted with Leu-19 antibody for CD56. The expression of CD56 in leukemia cells was not significantly affected by 12-O-tetradecanoylphorbol-13-acetate (TPA). By contrast, all hematopoietic materials were negative for CD57, while non-hematopoietic neuroblastoma cell lines expressed this molecule (4/5) as well as CD56 (5/5). Cytogenetically, the NCAM gene is located at chromosome 11q23, and chromosome breaks were often observed at this location in various leukemias. Blasts from all five acute non-lymphocytic leukemia (ANLL) patients and cell lines with 11q23-proximal chromosomal breaks were positive, while those from one ALL patient with an 11q23 abnormality were negative for CD56, necessitating further studies to clarify the link between the 11q23 abnormality and CD56 expression.     

Biosynthesis of granule proteins in normal human bone marrow cells. Gelatinase is a marker of terminal neutrophil differentiation

Differentiation and maturation of myeloid cells is characterized by the sequential acquisition of two distinct cytoplasmic granule subsets, azurophil granules and specific granules. We recently showed the existence of a third granule subset, gelatinase granules. To investigate whether appearance of gelatinase granules marks a further step in maturation of myeloid cells beyond the appearance of specific granules, we sorted normal human bone marrow cells into one of three groups according to maturity by centrifugation on Percoll density gradients. The biosynthesis of myeloperoxidase (MPO) (an azurophil granule marker), lactoferrin and neutrophil gelatinase-associated lipocalin NGAL (specific granules markers) and gelatinase was then studied in each of these groups. We found that gelatinase was synthesized mainly in the group containing band cells and segmented cells. This contrasted with lactoferrin and NGAL, which were synthesized almost exclusively in the group containing myelocytes and metamyelocytes, and with MPO, which was mainly synthesized in the group containing myeloblasts and promyelocytes. Immunocytochemistry was in full agreement with the biosynthesis data, and showed that gelatinase appears in band cells, whereas NGAL and lactoferrin both appear in myelocytes. Thus, acquisition of gelatinase granules marks a step in neutrophil differentiation beyond the appearance of specific granules.     

Evidence for distinct lymphocytic and monocytic populations in a patient with terminal transferase--positive acute leukemia.

Two distinct cell populations with lymphoblastic and monocytic characteristics were separated and characterized by multiple cell markers in a patient with terminal transferase-positive acute acute leukemia. The clinical course and sequential cell marker studies were consistent with the interpretation of a defect at the level of a common stem cell giving rise to a terminal transferase--positive lymphoblastic cell population at diagnosis and, following initial therapy, a terminal transferase--negative monocytic population.     

Expression of human B cell-associated antigens on leukemias and lymphomas: a model of human B cell differentiation

A series of monoclonal antibodies that define B cell restricted and associated antigens was utilized in an attempt to characterize tumors of B lineage and to relate these tumors to B cell differentiative stages. Antigens that were previously shown to be B cell restricted on normal B lymphocytes were similarly expressed only on B cell malignancies. In contrast, antigens that were B cell associated were also found on tumors of other lineages. Moreover, on the basis of cell surface phenotypes, tumors of B cell origin were divided into three major subgroups, which corresponded to the level of differentiation of the malignant tumor cell: pre-B cell stage (non-T acute lymphoblastic leukemia and chronic myelocytic leukemia in lymphoid blast crisis); the mid-B cell stage (chronic lymphocytic leukemia, poorly differentiated lymphomas); and secretory B cell stage (large cell lymphomas and plasma cell tumors). A hypothetical model is derived that relates the malignant B cell to its normal cellular counterpart on the basis of cell surface expression of this panel of B cell-restricted and B cell- associated antigens.     

DEC1 nuclear expression: a marker of differentiation grade in hepatocellular carcinoma

AIM: To investigate the expression patterns of human differentiated embryo chondrocyte 1 (DEC1) in hepatocellular carcinoma (HCC) and corresponding adjacent non-tumor and the normal liver tissues, the association between DEC1 expression and histopathological variables and the role of DEC1 in hepatocarcinogenesis. METHODS: The expression of DEC1 was detected immunohistochemically in 176 paraffin-embedded sections from 63 patients with HCC and 50 subjects with normal liver tissues. RESULTS: DEC1 protein was p...